Device and system for in-vivo imaging

ABSTRACT

The present invention provides a system and method for obtaining in vivo images. The system contains an imaging system and a transmitter for transmitting signals from a camera to a receiving system located outside a patient.

PRIOR APPLICATION DATA

This application is a continuation application of prior U.S. applicationSer. No. 11/295,491, filed on Dec. 7, 2005, entitled “DEVICE AND SYSTEMFOR IN VIVO IMAGING”, which in turn is a continuation application ofprior U.S. application Ser. No. 09/800,470, filed on Mar. 8, 2001, nowU.S. Pat. No. 7,009,634, entitled “DEVICE FOR IN-VIVO IMAGING”, which inturn claims benefit from prior U.S. provisional application no.60/187,883, filed on Mar. 8, 2000, entitled “IN VIVO IMAGING DEVICE ANDSYSTEM”, all of which are being incorporated by reference herein intheir entirety.

FIELD OF THE INVENTION

The present invention relates to an in vivo imaging device and systemsuch as for imaging the digestive tract.

BACKGROUND OF THE INVENTION

Among known in vivo measuring systems are endoscopes, which are oftenutilized to provide images of the upper or lower gastro-intestinaltract. However, endoscopes do not provide views of the entire length ofthe small intestines. Additionally, they are uncomfortable, may causedamage to the patient and are complex to operate.

Swallowable electronic capsules which are moved through the digestivetract through the action of digestion and which collect data andtransmit the data to a receiver system are known, one such example isthe “Heidelberg” capsule. Yet another example is a capsule disclosed inU.S. Pat. No. 5,604,531. These capsules may be utilized to measure pH,temperature and pressure throughout the intestines.

SUMMARY OF THE INVENTION

The device and system of the present invention enable obtaining in vivoimages from within body lumens or cavities, such as images of the entirelength of the gastrointestinal (GI) tract. The device and system containan imaging system that includes a complementary metal oxidesemiconductor (CMOS) imaging camera. The device also contains an ultralow power radio frequency (RF) transmitter for transmitting signals fromthe CMOS imaging camera to a receiving system.

The CMOS imaging camera is an ultra low power imager, has lowsensitivity to the red spectrum and is provided in chip scale packaging(CSP). The transmitter is an ultra low power RF transmitter with highbandwidth input, possibly provided in chip scale packaging.

The high integration and low power consumption achieved by the imagingsystem of the device and system of the invention were unobtainable priorto the advances in CMOS technology. Further, an ultra low power, highbandwidth input transmitter for video signals is unknown in the art.Also, an RF product in CSP has not been previously disclosed in the art.

Further, the imaging system may utilize a white light emitting diode(LED) as a light source rather than a reddish incandescence miniaturebulb or an RGB LED presently used in the art. The white LED enables toproduce a higher quality and more pleasant to the eye image.

There is therefore provided, in accordance with an embodiment of theinvention, an in vivo imaging device. The device consists of at leastone imaging system for producing video output, preferably digitaloutput, and a transmitter which transmits the video output to areceiving system.

The imaging system includes a CMOS imaging camera, at least oneillumination source for illuminating an in vivo site and an opticalsystem for imaging the in vivo site onto the CMOS imaging camera. Theillumination source may be a white LED. The term “white LED” as referredto herein relates to a combination of a blue LED chip (emitting light inthe blue spectrum range) and a refracting crystal. The blue LED chip isencapsulated within the refracting crystal such that blue light incidenton the crystal is emitted in different spectrums, resulting in whitelight. The white light emitted from the refracting crystal has a smallfraction of red light and an even smaller, almost nonexistent, fractionof infra red (IR) light.

The illumination source may be a specific integrated light source inwhich a refracting crystal matrix has a plurality of blue LED chipsintegrated therein.

The components of the device are harbored in a housing having an opticalwindow. The housing is configured for being inserted and passing throughbody lumens or cavities.

Also provided, in accordance with an embodiment of the invention, is asystem for in vivo imaging, which includes an imaging system producingvideo output, preferably digital output, a transmitter which transmitsthe video output of the imaging system and a receiving system forreceiving the transmitted video output. The imaging system consists of aCMOS imaging camera, an illumination source for illuminating an in vivosite and an optical system for imaging the in vivo site onto the CMOSimaging camera.

The system may further comprise an antenna array capable of surroundinga body and comprising one or a plurality of antennas for receiving thetransmitted video output and for producing a plurality of receivedsignals. Also the system may include a demodulator capable oftransforming the plurality of received video signals into a single videodatastream. The system may also comprise a data processing system whichgenerates tracking and video data from the single datastream.

The receiving system and data processor are typically located outside apatient.

Optionally, the system can also include an apparatus for operating thetransmitter intermittently.

In one embodiment of the invention, the device is a swallowable capsulehaving an optical window and containing an imaging system for obtainingin vivo images of the entire length of the GI tract and a transmitterwhich transmits the obtained images to a receiving system.

The imaging system consists of a CMOS imaging camera, a white LED and alens for imaging a GI tract site onto the CMOS imaging camera. Theswallowable capsule also includes a contained energy source forproviding energy the entirety of the electrical elements of the capsule.

Also provided in accordance with an embodiment of the invention is atransmitter for transmitting signals on RF to a receiving system. Thetransmitter, which is controlled by a normally opened (NO) switch,includes a control block for controlling the illumination and imager ofthe device of the invention.

The NO switch is controlled by an external magnet that keeps the switchclosed while it is in proximity to the switch. However, an internalblock maintains the logistics of an open switch, so as to keep thetransmitter circuits and all capsule main subsystems inactive while theexternal magnet is present. Removal of the external magnet causes theswitch to open and the internal block to close, thereby allowing thetransmitter circuits and capsule main subsystems to be activated.

Further provided is a method for obtaining images in vivo. The methodincludes the steps of: illuminating a site in vivo; collecting remittedlight onto pixels of a CMOS imaging camera, thereby generating an analogsignal; processing and converting the analog signal to a digital signal;randomizing the digital signal; transmitting the digital signal to areceiving system; and processing the transmitted signals to obtainimages of the in vivo site.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be understood and appreciated more fully fromthe following detailed description taken in conjunction with thedrawings in which:

FIG. 1 is a schematic longitudinal cross section illustration of an invivo imaging device according to an embodiment of the invention;

FIG. 2 is a schematic presentation of the CMOS imaging camera accordingto an embodiment of the invention;

FIG. 3 is a cross section schematic illustration of a device, inaccordance with an embodiment of the invention, including a specificintegrated illumination source;

FIG. 4 is a block diagram of the transmitter in accordance with anembodiment of the invention; and

FIG. 5 is a block diagram presentation of the method according to anembodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The device and system of the invention are utilized for viewing insidebody lumens and cavities and for transmitting at least video data.

Reference is now made to FIG. 1 which illustrates the device and itscomponents, according to an embodiment of the invention. The device 10typically comprises an optical window 21 and an imaging system forobtaining images from inside a body lumen, such as the GI tract. Theimaging system includes an illumination source 23, such as a white LED,a CMOS imaging camera 24, which detects the images and an optical system22 which focuses the images onto the CMOS imaging camera 24. Theillumination source 23 illuminates the inner portions of the body lumenthrough optical window 21. Device 10 further includes a transmitter 26and an antenna 27 for transmitting the video signal of the CMOS imagingcamera 24, and a power source 25, such as a silver oxide battery, thatprovides power to the electrical elements of the device 10.

It will be appreciated that a plurality of CMOS imaging cameras may beused in the device and system of the invention. Each CMOS imaging cameramay include its own optical system and either one or more illuminationsources, in accordance with specific requirements of the device orsystem.

Images obtained by the CMOS camera 24 are transmitted to a receivingsystem (not shown), which may also include a data processing unit. Thereceiving system and data processing unit are typically located outsidea patient.

The device 10 is capsule shaped, can be easily swallowed and maypassively pass through the entire GI tract, pushed along by naturalperistalsis.

Nonetheless, it should be appreciated that the device may be of anyshape suitable for being inserted into and passing through a body lumenor cavity. Furthermore, the device of the invention may be attached oraffixed on to an instrument that is inserted into body lumens andcavities, such as on an endoscope, laparoscope, stent, needle, catheteretc.

Thus, the device may be introduced into a body lumen or cavity byswallowing, by using an endoscopic device, by surgery and so on.

A suitable CMOS imaging camera 24 is, for example, a “camera on a chip”type CMOS imager specified by Given Imaging Ltd. of Yokneam, Israel anddesigned by Photobit Corporation of California, USA, with integratedactive pixel and post processing circuitry (as will be further describedwith reference to FIG. 2). The single chip camera can provide eitherblack and white or color signals.

The CMOS imaging camera 24 is designed such that it is less sensitive tolight in the red spectrum than known CMOS cameras.

The optical system 22 comprises at least one lens and optionally mirrorsand/or prisms for collecting and collimating remitted light on to thepixels of the CMOS imaging camera 24. Typically, the optical systemcomprises an aspherical focussing lens. A suitable lens is, for example,the lens designed by Given Imaging Ltd. of Yokneam, Israel, inaccordance with specific object plane, distortion and resolutionparameters.

Illumination source 23, transmits illumination to the walls of the bodylumen via the optical window 21. The lens of the optical system 22 thenfocuses remittent light onto the pixels of the CMOS imaging camera 24.

A single or plurality of light sources or a specific integrated lightsource may be used and positioned in accordance with specific imagingrequirements, such as to avoid stray light etc. Also, the optical window21 may be positioned and shaped according to the device shape andaccording to specific imaging requirements. For example, optimizedimaging conditions can be obtained when optical window 21 is formed todefine an ellipsoid shaped dome and the CMOS imaging chip camera system24 and illumination sources 23 are positioned in the proximity of thefocal plane of the shape defined by the optical dome. Obtaining theabove imaging conditions is described in WO 00/76391, which is assignedto the common assignees of the present invention and which is herebyincorporated in its entirety by reference.

The in vivo sites imaged in the present invention are usually very closeto the imager. For example, an 11×30 mm capsule passing through andimaging the small intestine, images the intestine walls from a veryshort distance. It is therefore possible to satisfy the illuminationrequirements of the imaging process utilizing solid state illuminationsources, such as LEDs.

In an embodiment of the invention the illumination source is a whiteLED. The white light emitted from the white LED has a small fraction ofred light and even smaller fraction of IR light. Hence, a white LED isbeneficial for use with silicone based image sensors (such as CMOSimaging cameras) because of the silicone sensitivity to red and IRlight.

In a system which includes the CMOS imaging camera of the invention withits reduced sensitivity to light in the red spectrum and a white LEDillumination source, no IR reject filters (photopic filters) are needed.

A suitable transmitter may comprise a modulator which receives the videosignal (either digital or analog) from the CMOS imaging camera, a radiofrequency (RF) amplifier, an impedance matcher and an antenna. Thetransmitter will be further illustrated in FIG. 4.

Other optional parts of the system as well as the method forlocalization of a capsule containing the system within the digestivesystem may be similar to those described in U.S. Pat. No. 5,604,531(which is assigned to the common assignees of the present invention andwhich is hereby incorporated in its entirety by reference).

Device 10 can additionally include sensor elements for measuring pH,temperature, pressure, etc. These sensor elements, some of which aredescribed in the prior art, may be any element suitable for measuringconditions prevailing in the body lumen (for example, the digestivesystem) and that are capable of being appended to or included in thedevice.

Reference is now made to FIG. 2, in which a schematic layout of the CMOSimaging camera is presented. The CMOS imaging camera 200 comprisesactive pixel and post processing circuitry on a single chip. The CMOSimaging camera 200 includes photo cell 202 (the pixels of the CMOSimaging camera), correlated double sampler (CDS) 204, analog to digital(A/D) converter 206, encoding and randomizing unit 208 and timinggenerator 210 for control and synchronization of the circuitry elements.

Light collected by an optical system is directed onto CMOS imagingcamera 200 and photons are converted to electrons as the light isabsorbed by photo cell 202. Electrons are converted to electricalcurrent and an analog signal is produced by the active pixel circuitry.The analog signal is conveyed for further processing by on-chip postprocessing circuitry. The signal is further processed by CDS 204. CDS204 performs correlated double sampling, for canceling noise and signalshaping before conveying the signal to the A/D converter 206. The A/Dconverter 206 is a serial output A/D converted which enables serial, lowpower transmission of signals. The signal is converted into a digitalsignal and is further conveyed to encoding and randomizing unit 208 fordefining frame and row parameters (encoding) and for priming the signalsfor transmission (randomizing) The encoding and randomizing unit 208randomizes the occurrence of the digital “0” and “1” signals such thattransmission is not impeded by a reoccurring signal of one type.

The CMOS imaging camera 200 is specified by Given Imaging Ltd. ofYokneam, Israel and designed by Photobit Corporation of California, USA,according to a specification adjusted to in vivo imaging. The CMOSimaging chip has ultra low power requirements (less than 3 milliwatts).The dynamics of the increase of dark current generated by the imagingcamera, as a function of temperature, is less than that of solid statedevices known in the art, such that at 37° C. a low fraction of the output video signal is dark current. Further, as discussed above, theimaging camera has reduced sensitivity to light in the red spectrum,abating the need for photopic filters.

Reference is now made to FIG. 3 in which a device for in vivo imagingcomprising a specific integrated light source is illustrated. Device 300comprises CMOS imaging camera 302, an optical system (not shown) forimaging in vivo images onto the CMOS imaging camera 302 and anintegrated light source 304 for illuminating a site in vivo. The device300 further includes a transmitter 305 for transmitting video data fromthe imaging camera 302 to a receiver (not shown). The transmitter 305generates a high voltage and current source for the light source 304.The integrated light source 304 is connected to the transmitter 305through connective wires 301. The electrical components of the deviceare powered by a battery contained within the device (not shown).

The integrated light source 304 comprises a strip 306 of a refractingcrystal matrix encircling the CMOS imaging camera 302. Blue LED chips308, encapsulated within the refracting crystal matrix of strip 306, arepositioned along the strip 306 such that illumination is provided in aring around the CMOS imaging camera 302.

Blue LED chips 308 can also be sprinkled throughout the strip 306 suchthat the whole strip 306 emits light.

Reference is now made to FIG. 4 in which a block diagram of thetransmitter is illustrated. The transmitter 400, an ASIC (applicationspecific integrated circuit) designed to fulfill internationalcommunication standards (such as the FCC) standards, operates on aminimum shift keying (MSK) modulation system to effect transmitting ofdigital signals through antenna 426 and 427 on radio frequencies to areceiving system. The transmitter 400 also controls the illumination andimager of the device of the invention and the logical conversion of theswitch (as described above). The transmitter 400 includes a one timeprogramming unit 408 in communication with external programming input428, a control logic block 401 for communicating with the imager, aphase lock loop (PLL) 402 in communication with modulator 425,optionally, a LED power and control block 403 for controlling theillumination, a main oscillator 404 and a switch 405 which controls aninternal electronic switch 406.

The control logic block 401 communicates with the imager, readspreprogrammed parameters and performs the interface to the “outside”world in the programming mode. Control logic block 401 maintains amaster clock, is synchronized by bit rate data 412 and frame rate 413,and through control 411, which is generated by the imager, triggers LEDpower and control block 403. Control logic block 401 further controlsthe master clock 414 and the imager shutdown 415.

During shutdown the transmitter sends out beacon signals only. Theshutdown enables economic use of the device's power supply. For example,in a device designed for imaging the small intestine, the transmitter400 may be programmed to include a two hour delay, during which periodshutdown of the imager and other device electronics is effected. Twohours is approximately the time it takes a swallowable device to passthe stomach and enter the small intestine, in particular patients. Thus,in those patients, the device will utilize power from the battery, forcollecting images, only when the device has reached the small intestine.

The PLL 402 is a feedback system intended to automatically correctdrifts in the transmitted frequency. PLL 402 includes a pre-scaler 424for fast frequency dividing that is not dependant on the channelfrequency. The pre-scaler 424 is in communication with a divider 421that divides the frequency of the oscillator 404 to perform thereference frequency for the PLL. The division value is channeldependant. The PLL 402 also includes a phase frequency detector (PFD)422 for performing the frequency comparison and the phase comparison ofthe PLL, and a charge pump 423 for performing the shape of the looptransmission of the whole loop.

LED power and control block 403 includes a high voltage source 432 thatis controlled by the external capacitor 431. LED power and control block403 also includes a high current source 433 and the peak current valueof the LEDs is controlled by the resistor which is connected to LedRes435.

The transmitter 400 is controlled by an external magnetic switch 405.The switch 405 is a normally opened (NO) switch that is kept closed byan external magnet, as described above. Switch 405 controls an internalelectronic switch 406 that controls all the device electronics.Electronic switch 406 includes a low leakage circuitry to convert thelogic of the NO switch 405 to “normally closed” (NC) logic, such thatalthough switch 405 is a NO switch it will keep the transmitter inactivewhile it is closed.

The low leakage circuit only uses 1%-3% of the battery power per year,so that the internal electronic switch 406 is not a significant factorin the power regimen of the device.

In an embodiment of the invention the device is a swallowable capsulehaving an optical window and comprising a CMOS imaging camera, whiteLEDs, an optical system, a transmitter and battery. The swallowablecapsule is kept inactive while contained in a package having a magnet,such as the magnetic packaging described in PCT application IL00/00752(which is assigned to the common assignee of the present invention andwhich is hereby incorporated in its entirety by reference). Just priorto use the package having the magnet is removed enabling the switch 405to be opened, thereby activating the transmitter and with it, initiatingimager and illumination operation.

The input bandwidth of the information in the transmitter 400 is over1.35 Megabit per second. Such a low powered high input bandwidthtransmitter for transmitting video data, has not yet been shown in theart.

Reference is now made to FIG. 5 in which a block diagram of the methodof the invention is illustrated. The method for in vivo imaging includesthe following steps: illuminating a site in vivo (502); collectingremitted light onto pixels of a CMOS imaging camera, thereby generatingan analog signal (504); converting the analog signal to a digital signal(506); randomizing the digital signal (508); transmitting the digitalsignal to a receiving system (510) and processing the transmittedsignals to obtain images of the in vivo site (512).

The step of illumination (502) is preferably carried out by employingwhite LEDs to illuminate the site in vivo. Illumination may becontinuous or alternating in accordance with specific requirements ofthe system.

Collecting light remitted from the site in vivo (504) and directing iton to the pixels of a CMOS imaging chip is achieved by employing anoptical system which comprises a lens and which may further comprise anysuitable collimator.

Conversion of the analog signal to a digital signal (506) is preferablyeffected in a serial manner.

Randomizing the digital signal (508), namely randomizing the occurrenceof the digital signals (“0” and “1”), is performed so that transmissionis not impeded by a reoccurring signal of one type.

Transmission of the signal (510) is accomplished using radio frequencies(approximately 432-434 Mhz) at a rate of two to eight frames per secondto an array of antennas attached to a patient's body. The antennas allowimage capture and are also used to calculate and indicate the positionof the imager in the patient's body. An example of the calculation andindication the position of the imager in the patient's body is providedin the above mentioned U.S. Pat. No. 5,604,531.

Processing of signals (512) can be carried out by employing suitableprocessors and software. For example, the RAPID software (proprietysoftware developed and owned by Given Imaging Ltd. of Yokneam, Israel)is used to obtain a video clip of images captured from within the GItract. The video clip can be synchronized with the trajectory of theimaging device as it passes through the GI tract to enable localizationof the device in the GI tract.

Additionally, a plurality of receiving antennas can be used which can bemoved to the location enabling best receiving conditions.

The images can be stored on a small portable recorder carried on a beltand subsequently downloaded for analysis and retrieval. Additionally,the receiver can be connected directly to a stationary data recorder.

Experiments were carried out with an 11×30 mm capsule comprising a CMOSimaging chip and miniature processor, white LED light sources, a shortfocal length lens and a miniature transmitter and antenna. The capsule,powered by silver oxide batteries, was swallowed and more than 5 hoursof continuous recording of images from the gastrointestinal tract wereachieved.

Live transmission of good quality video images were obtained for up to 6hour periods in ambulatory dogs.

With ethical committee approval a human volunteer study was performed.The capsule was easily swallowed. Moving images were obtained from thestomach and small intestine. No discomfort was experienced. The opticalwindow remained clear throughout the whole transmission.

Trigonometric analysis of signal strength allowed continuous monitoringof the capsule position. Imaging of the small bowl was successfullycompleted in 2 hours.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather the scope of the present invention isdefined only by the claims which follow:

1. A swallowable capsule for in-vivo imaging of the gastrointestinaltract, said capsule comprising: a housing, said housing comprising adome shaped optical window disposed along a longitudinal axis of saidcapsule, said housing enclosing at least: a CMOS imaging camera; atleast two white LED illumination sources for illuminating agastrointestinal tract site directly through said optical window; anoptical system, centered along said longitudinal axis, comprising atleast one lens, for collecting light from said gastrointestinal tractsite directly through said optical window onto said CMOS imaging camera;wherein said optical system and at least two white LED illuminationsources are separated from said dome shaped optical window by a gap, andthe at least two white LED illumination sources are disposed around saidoptical system and not on said longitudinal axis; and a transmitter fortransmitting the signal of the CMOS imaging camera to a receivingsystem.
 2. The swallowable capsule of claim 1 wherein the at least twowhite LED illumination sources are positioned in the same plane as theoptical system.
 3. The swallowable capsule of claim 1 wherein the atleast two white LED illumination sources and the optical system arepositioned substantially behind the optical window.
 4. The swallowablecapsule of claim 1 wherein the at least two white LED illuminationsources and the lens are positioned at the base of the optical window.5. The swallowable capsule of claim 1 wherein the illumination by the atleast two white LED illumination sources is alternating.
 6. Theswallowable capsule of claim 1 wherein the dome shaped optical window isformed to define an ellipsoid shape.
 7. The swallowable capsule of claim1 wherein the CMOS imaging camera has reduced sensitivity to light inthe red spectrum.
 8. The swallowable capsule of claim 1 wherein thetransmitter transmits at a rate of two to eight frames per second. 9.The swallowable capsule of claim 1 wherein the housing comprises anelongated, circular cylindrical portion and two dome shaped portions,the base of each dome shaped portion positioned at a base of thecylindrical portion; wherein said dome shaped optical window comprisesone of said dome shaped portions; and wherein the central axis of saidcylindrical portion defines said longitudinal axis of said capsule. 10.The swallowable capsule of claim 1 wherein the at least two white LEDillumination sources are positioned in the proximity of the focal planeof the shape defined by the optical window.